The metabolism of prostaglandins either results in their biological inactivation or in a conversion to another class of prostaglandins with somewhat different physiological properties. Prostacyclin and thromboxane A2 are spontaneously labile at a physiologic pH, but there is some evidence to suggest that they also are metabolized. The objective of the proposed research is to study the enzymes catalyzing prostaglandin, prostacyclin, and thromboxane metabolism in the human placenta. The NAD-linked 15-hydroxyprostaglandin dehydrogenase, NADP-linked 15-hydroxyprostaglandin dehydrogenase (9-ketoprostaglandin reductase), 15-ketoprostaglandin delta 13-reductase, omega-oxidase, specific prostacyclin or thromboxane enzymes (if they exist) and the peptide inhibitor of the NADP-linked 15-hydroxyprostaglandin dehydrogenase will be measured in placental tissue to determine whether their levels correlate with the onset of labor or the development of pathologic processes (e.g., toxemia or hydramnios). The enzyme and peptide inhibitors will be isolated and purified, their characteristics will be established, and the mechanisms controlling their activity will be sought. In an attempt to develop more effective prostaglandin inhibitors, various synthetic prostaglandin, prostacyclin and thromboxane analogs will be tested using highly purified placental enzymes. The enzymes isolated from human placenta will be compared with the same enzymes from other species to determine whether there is species or organ specificity.